Proximal femoral bone strength is not only a function of femoral bone mineral density (BMD), but also a function of the spatial distribution of bone mass intrinsic in structural geometric properties ...such as diameter, area, length, and angle of the femoral neck. Recent advancements in bone density measurement include software that can automatically calculate a variety of femoral structural variables that may be related to hip fracture risk. The purpose of this study was to compare femoral bone density, structure, and strength assessments obtained from dual-energy X-ray absorbtiometry (DXA) measurements in a group of women with and without hip fracture.
DXA measurements of the proximal femur were obtained from 2,506 women 50 years of age or older, 365 with prior hip fracture and 2,141 controls. In addition to the conventional densitometry measurements, structural variables were determined using the Hip Strength Analysis program, including hip axis length (HAL), cross-sectional moment of inertia (CSMI), and the femur strength index (FSI) calculated as the ratio of estimated compressive yield strength of the femoral neck to the expected compressive stress of a fall on the greater trochanter.
Femoral neck BMD was significantly lower and HAL significantly higher in the fracture group compared with controls. Mean CSMI was not significantly different between fracture patients and controls after adjustment for BMD and HAL. FSI, after adjustment for T score and HAL, was significantly lower in the fracture group, consistent with a reduced capacity to withstand a fall without fracturing a hip.
We conclude that BMD, HAL, and FSI are significant independent predictors of hip fracture.
The lagomorph‐infecting Treponema paraluisleporidarum is a close relative of the human syphilis‐bacterium Treponema pallidum. There is a paucity of information on the epidemiology of hare syphilis ...and its relationship to the rabbit‐ and human‐infecting treponemes that cause syphilis. In our study, we tested 734 serum samples from European brown hares (Lepus europaeus) collected between 2007 and 2019 in the federal state of Lower Saxony, Germany, for the presence of antibodies against T. paraluisleporidarum. Since T. paraluisleporidarum cross‐reacts with T. pallidum antigen, we used a commercially available T. pallidum‐particle agglutination (TP‐PA) assay to test for the presence of antibodies. A high seropositivity (n = 405/734) was detected. An additional 233 serum samples were retested using a fluorescent treponemal antibody absorption test to confirm the results of the TP‐PA assay. Our results show that infection is widespread in Lower Saxony and suggest a horizontal (sexual) transmission mode since adult hares show significantly higher seropositivity than subadults (odds ratio: 0.03 95% CI 0.02–0.05, p < .0001). No difference was detected based on gender (odds ratio: 0.79 95% Cl 0.58–1.07, p = .1283). Further studies are warranted to genetically characterize the T. paraluisleporidarum strains that infect wild hares.
A brief exposure to systemic hypoxia (i.e., hypoxic preconditioning; HPC) prior to transient middle cerebral artery occlusion (tMCAo) reduces infarct volume, blood-brain barrier disruption, and ...leukocyte migration. CCL2 (MCP-1), typically regarded as a leukocyte-derived pro-inflammatory chemokine, can also be directly upregulated by hypoxia-induced transcription. We hypothesized that such a hypoxia-induced upregulation of CCL2 is required for HPC-induced ischemic tolerance.
Adult male SW/ND4, CCL2-null, and wild-type mice were used in these studies. Cortical CCL2/CCR2 message, protein, and cell-type specific immunoreactivity were determined following HPC (4 h, 8% O2) or room air control (21% O2) from 6 h through 2 weeks following HPC. Circulating leukocyte subsets were determined by multi-parameter flow cytometry in naïve mice and 12 h after HPC. CCL2-null and wild-type mice were exposed to HPC 2 days prior to tMCAo, with immunoneutralization of CCL2 during HPC achieved by a monoclonal CCL2 antibody.
Cortical CCL2 mRNA and protein expression peaked at 12 h after HPC (both p < 0.01), predominantly in cortical neurons, and returned to baseline by 2 days. A delayed cerebral endothelial CCL2 message expression (p < 0.05) occurred 2 days after HPC. The levels of circulating monocytes (p < 0.0001), T lymphocytes (p < 0.0001), and granulocytes were decreased 12 h after HPC, and those of B lymphocytes were increased (p < 0.0001), but the magnitude of these respective changes did not differ between wild-type and CCL2-null mice. HPC did decrease the number of circulating CCR2+ monocytes (p < 0.0001) in a CCL2-dependent manner, but immunohistochemical analyses at this 12 h timepoint indicated that this leukocyte subpopulation did not move into the CNS. While HPC reduced infarct volumes by 27% (p < 0.01) in wild-type mice, CCL2-null mice subjected to tMCAo were not protected by HPC. Moreover, administration of a CCL2 immunoneutralizing antibody prior to HPC completely blocked (p < 0.0001 vs. HPC-treated mice) the development of ischemic tolerance.
The early expression of CCL2 in neurons, the delayed expression of CCL2 in cerebral endothelial cells, and CCL2-mediated actions on circulating CCR2+ monocytes, appear to be required to establish ischemic tolerance to focal stroke in response to HPC, and thus represent a novel role for this chemokine in endogenous neurovascular protection.
Objective
To evaluate the feasibility of 2D-perfusion angiography (2D-PA) in order to quantify perfusion changes of the lung parenchyma pre- and post-balloon pulmonary angioplasty (BPA).
Methods
...Thirty consecutive interventions in 16 patients with 99 treated pulmonary artery segments were included. To quantify changes in pulmonary blood flow using 2D-PA, the acquired digital subtraction angiographies (DSA) pre- and post-BPA were post-processed. A reference ROI in the treated pulmonary artery and a distal target ROI in the lung parenchyma were placed in corresponding areas on DSA pre- and post-BPA. Time to peak (TTP), peak density (PD) and area under the curve (AUC) were assessed. The ratios reference ROI to target ROI (TTP
parenchyma
/TTP
inflow
; PD
parenchyma
/PD
inflow
; AUC
parenchyma
/AUC
inflow
) were calculated. Relative differences of the 2D-PA parameters were correlated to changes in the pulmonary-flow-grade-score.
Results
The pulmonary-flow-grade-score improved after BPA (p<0.0001). Likewise, the ratio TTP
parenchyma
/TTP
inflow
shortened by 10% (p=0.0002), the PD
parenchyma
/PD
inflow
increased by 46% (p<0.0001) and the AUC
parenchyma
/AUC
inflow
increased by 36% (p<0.0001). A significant correlation between changes in the pulmonary-flow-grade-score and changes in PD
parenchyma
/PD
inflow
(ρ=0.48, p<0.0001) and AUC
parenchyma
/AUC
inflow
(ρ=0.31, p=0.0018) was observed.
Conclusion
Quantification of pulmonary perfusion pre- and post-BPA using 2D-PA is feasible and has the potential to improve monitoring of BPA.
Key points
• Quantification of BPA results by use of 2D-PA is feasible.
• 2D-PA allows objective assessment of changes in lung parenchymal perfusion.
• 2D-PA has the potential to optimize BPA.
Protection of the blood–brain barrier (BBB) is correlated with improved outcome in stroke. Sphingosine kinase (SphK)-directed production of sphingosine-1-phosphate, which we previously documented as ...being vital to preconditioning-induced stroke protection, mediates peripheral vascular integrity via junctional protein regulation. We used a hypoxic preconditioning (HPC) model in adult wild-type and SphK2-null mice to examine the isoform-specific role of SphK2 signaling for ischemic tolerance to transient middle cerebral artery occlusion and attendant BBB protection. Reductions in infarct volume and BBB permeability in HPC-treated mice were completely lost in SphK2-null mice. Hypoxic preconditioning-induced attenuation of postischemic BBB disruption in wild types, evidenced by reduced extravascular immunoglobulin G intensity, suggests direct protection of BBB integrity. Measurement of BBB junctional protein status in response to HPC revealed SphK2-dependent increases in triton-insoluble claudin-5 and VE-cadherin, which may serve to strengthen the BBB before stroke. Postischemic loss of VE-cadherin, occludin, and zona occludens-1 in SphK2-null mice with prior HPC suggests that SphK2-dependent protection of these adherens and tight junction proteins is compulsory for HPC to establish a vasculoprotective phenotype. Further elucidation of the mediators of this endogenous, HPC-activated lipid signaling pathway, and their role in protecting the ischemic BBB, may provide new therapeutic targets for cerebrovascular protection in stroke patients.
In this paper, the authors investigate whether better information about the macroeconomic environment of an economy has a positive impact on its capital inflows, namely portfolio and foreign direct ...investment (FDI). The purpose of the study is to explicitly quantify information asymmetries by compliance with the IMF's Special Data Dissemination Standard (SDDS). The authors find that compliance with the SDDS increased FDI inflows by an economically relevant magnitude of 56 % while there are no such aggregate effects for portfolio flows. The empirical strategy demonstrates that the effect runs from SDDS to FDI and not vice versa, introduces a test for endogeneity bias due to omitted variables, and tests for spatial correlation in the residuals.
The aim of this study was the development and evaluation of a real-time guidance support using optical Moiré Phase Tracking (MPT) for magnetic resonance (MR) guided percutaneous interventions. A ...gradient echo sequence, capable of real-time position updates by the MPT system, was modified to enable needle guidance based on four rigidly attached MPT markers at the back of a needle. Two perpendicular imaging planes were automatically aligned along the calibrated needle and centered at its tip. For user guidance, additional information about the needle trajectory and the tip to target distance were added as image overlay. Both, images and guiding information were displayed on the in-room monitor to facilitate MR guided interventions. The guidance support was evaluated by four experienced interventional radiologists and four novices targeting rubber O-rings embedded in a custom-made phantom on a 3T wide-bore MRI system (80 punctures). The skin to target time, user error, system error and total error were analyzed. The mean skin to target time was 146s±68s with no statistically significant difference between experts and novices. A low mean user error (0.91mm±0.43mm), system error (0.53mm±0.27mm) and total error (0.99mm±0.47mm) was reached in all directions. No statistically significant difference in user error, system error and total error could be found between experts and novices. The presented tracking and image guidance system combined with the user interface offers continuous and interactive control of the imaging plane while puncturing in the magnet enabling accurate real-time feedback for both, experienced and non-experienced users.
Percutaneous hepatic perfusion (PHP) delivers high-dose melphalan to the liver while minimizing systemic toxicity via filtration of the venous hepatic blood. This two-center study aimed to examine ...the safety, response to therapy, and survival of patients with hepatic-dominant metastatic uveal melanoma (UM) treated with PHP. A total of 66 patients with liver-dominant metastasized uveal melanoma, treated with 145 PHP between April 2014 and May 2020, were retrospectively analyzed with regard to adverse events (AEs; CTCAE v5.0), response (overall response rate (ORR)), and disease control rate (DCR) according to RECIST1.1, as well as progression-free and overall survival (PFS and OS). With an ORR of 59% and a DCR of 93.4%, the response was encouraging. After initial PHP, median hepatic PFS was 12.4 (confidence interval (CI) 4-18.4) months and median OS was 18.4 (CI 7-24.6) months. Hematologic toxicity was the most frequent AE (grade 3 or 4 thrombocytopenia after 24.8% of the procedures); less frequent was grade 3 or 4 hepatic toxicity (increased aspartate transaminase (AST) and alanine transaminase (ALT) after 7.6% and 6.9% of the interventions, respectively). Cardiovascular events included four cases of ischemic stroke (2.8%) and one patient with central pulmonary embolism (0.7%). In conclusion, PHP is a safe and effective salvage treatment for liver-dominant metastatic uveal melanoma. Serious AEs-though rare-demand careful patient selection.
To evaluate mosaic perfusion patterns and vascular lesions in patients with chronic thromboembolic pulmonary hypertension (CTEPH) using C-Arm computed tomography (CACT) compared to computed ...tomography pulmonary angiography (CTPA). We included 41 patients (18 female; mean age 59.9 ± 18.3 years) with confirmed CTEPH who underwent CACT and CTPA within 21 days (average 5.3 ± 5.2). Two readers (R1; R2) independently evaluated datasets from both imaging techniques for mosaic perfusion patterns and presence of CTEPH-typical vascular lesions. The number of pulmonary arterial segments with typical findings was evaluated and the percentage of affected segments was calculated and categorized: < 25%; 25-49%; 50-75%; < 75% of all pulmonary arterial segments affected by thromboembolic vascular lesions. Inter-observer agreement was calculated for both modalities using the intraclass-correlation-coefficient (ICC). Based on consensus reading the inter-modality agreement (CACT
vs. CTPA
) was calculated using the ICC. Inter-observer agreement was excellent for central vascular lesions (ICC > 0.87) and the percentage of affected segments (ICC > 0.76) and good for the perceptibility of mosaic perfusion (ICC > 0.6) and attribution of the pattern of mosaic perfusion (ICC > 0.6) for both readers on CACT and CTPA. Inter-modality agreement was excellent for the perceptibility of mosaic perfusion (ICC = 1), the present perfusion pattern (ICC = 1) and central vascular lesions (ICC = 1). However, inter-modality agreement for the percentage of affected segments was fair (ICC = 0.50), with a greater proportion of identified affected segments on CACT
. CACT demonstrates a high agreement with CTPA regarding the detection of mosaic perfusion. CACT detects a higher number of peripheral vascular lesions compared to CTPA.
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